Creative Biostructure provides custom MemPro™ gene-to-structure services for Neutral/alkaline ceramidases.
Ceramidases are a kind of enzymes that cleave fatty acids from ceramide, generating sphingosine (SPH) which in turn is phosphorylated by a sphingosine kinase to form sphingosine-1-phosphate (S1P) (Figure 1). The biological functions of ceramide, SPH, and S1P are the mediation of cell proliferation, differentiation, apoptosis, adhesion, and migration. In other words, ceramidases play a key role in sphingolipid metabolism by hydrolyzing ceramide into sphingosine. Nowadays, 7 human ceramidases encoded by 7 distinct genes have been reported, including acid ceramidase (ASAH1, is a lysosomal enzyme and functions in cell survival), neutral ceramidases (ASAH2, ASAH2B and ASAH2C, function in protection against inflammatory cytokines), alkaline ceramidases (ACER1 functions in mediating cell differentiation by controlling the generation of SPH and S1P, ACER2 functions in cell proliferation and survival, the function of ACER3 is unknown). Neutral/alkaline ceramidases hydrolyze asphingolipid ceramide into the corresponding sphingosines and free fatty acids at an optimal pH of 6.5-8.5. They play a key role in the sphingolipid signaling pathway by producing sphingosine molecules at the cell surface.
Figure 1. Schematic diagram of ceramidase hydrolysis process.
Sphingosines involved in the biosynthesis of sphingosine 1-phosphate, which is an anti-apoptotic factor, thus suggesting its bioactivity in the prevention of apoptosis. It is predominately expressed in the intestine and also expressed with high levels in kidney and skeleton muscle. Sphingosines can be phosphorylated by the sphingosine kinase activity to sphingosine 1-phosphate (SPP), which besides to act as extracellular ligand, can behave as intracellular mediator, accounting at least in part for the mitogenic activity exerted by platelet derived growth factor (PDGF). The neutral/alkaline isoform of ceramidase in signal transduction: The enzymatic activity has been shown to be simulated by PDGF in rat mesangial cells and by low concentration of interleukin 1β (IL-1β) in rat hepatocytes.
Creative Biostructure can provide various custom MemPro™ gene-to-structure services for membrane protein family, including the identification, isolation, purification, stabilization, and crystallization of membrane proteins of your interest. Please feel free to contact us for a detailed quote.
C. Mao and L. M. Obeid (2008). Ceramidases: regulators of cellular responses mediated by ceramide, sphingosine, and sphingosine-1-phosphate. Biochim. Biophys. Acta., 1781 (9): 424–434.
E. Romiti, et al. (2000). Neutral/alkaline and acid ceramidase activities are actively released by murine endothelial cells. Biochem. Bioph. Res. Co., 275: 746-751.